ImmunologyUnitDepartmentofPathology

CollegeofMedicineKingSaudUniversity

Dr.SamiaTowfeek AL-ShouliClinicalImmunologyandAllergy

ReferenceKuby Immunology7th Edition

2013Chapter15Pages485-510

Objectives• Toknowthathypersensitivityreactionsareoverandexcessive

immuneresponsesthatcanbeharmfultobodyinfourdifferentways

• TobefamiliarwithinflammatoryprocessesinTypeIhypersensitivityreactionthatmediatesallergicinflammation

• TorecognizethatTypeIIhypersensitivitydealswithimmuneresponsesagainstantigensthatareintegralpartofcellmembraneandareusuallyassociatedwithautoimmunedisorders

• ToknowthatTypeIIIhypersensitivityreactionsaremediatedbyimmunecomplexesandcausevasculitis

• TodescribeTypeIVhypersensitivityisapurelycellmediatedimmuneresponseassociatedwithchronicinflammation

Whatishypersensitivity?

• Protective immunity:desirablereaction

• Hypersensitivity:undesirablereaction

• Undesirableresponsescanbemediatedby– Antibody binding toantigens(TypesI-III)– Cell mediatedreaction tochemicalsorproteins(TypeIV)

GelandCoombsClassification

Type I: IgE Ab

Type II: IgGAb to tissue

antigens

Type III: IgG

Immune Complexes

Type IV: Cell Mediated Immunity

TypeI:ImmediateHypersensitivity

n Mostpeoplewillnotreacttotheseallergensbutsomeindividuals“atopic”respondbyproducinglargeamountsofIgE inresponsetothoseotherwiseharmlesssubstances

n Non-allergic individuals respond to theseallergens by producing IgG antibodies

Type I Hypersensitivity• Also termed as:

Immediate Hypersensitivity

Allergic reactions

Anaphylactic reactions are severe and rapidly progressing systemic forms which can be quickly life threatening

(Occurs within minutes to hours)

Features

- Antibody type: IgE

- Cellular components: Mast cells, basophiles & eosinophils

- Antigens:Also known as allergens (antigens with low molecular weight & highly soluble)

Allergensn SomeoftheallergensinvolvedintypeIhypersensitivityare:pollens,dustmiteallergens,animaldander,nuts,shellfish,variousdrugsetc

Type I Reaction occur in 2 phases:

• Phase I :- Sensitization phase .

Allergen enter tissues , induce an immune response . B – cells transformto plasma cells & produce IgE.

- IgE bind to receptors on Mast cells andbasophiles ( F c ЄRI - high affinity receptors).

individuals become :

“ Sensitized . “

Type I reactions occur in two phases

• Phase I :- Sensitization phase .

Allergen enter tissues , induce an immune response . B – cells transformto plasma cells & produce IgE.

- IgE bind to receptors on Mast cells andbasophiles ( F c ЄRI - high affinity receptors).

individuals become :

“ Sensitized . “

- Sensitization phase First contact with allergens

- Challenge phaseSubsequent contact with allergens

TypeIHypersensitivity(Immediate)

Sensitization

Challenge

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PrimaryandSecondaryMediators

Allergyisasystemicdisorder

NosePharynx

Stomach

EsophagusLungs

Skin

Foodallergy

AllergicrhinitisAsthma

EczemaUrticariaAllergicdermatitis

Allergy:Rhinitis,Eczema&Conjunctivitis

Normalnose

* Injected allergens:

Hymenoptera (bees, wasps, ants) sting venom enters the blood stream

à Systemic inflammation

à Anaphylactic shock(life - threatening)

vAnaphylactoid reactions:-Are non - IgE mediatedmay result from contrast media orlocal anesthetics

Skin Prick testDiagnosisofAllergy

1. Skin prick test (SPT)

2. Specific IgE measurement (RAST)

3. Elimination / Provocation test (Food allergy)

• Features:-- IgG (orIgM)- Antigens:boundtocellmembranes

(Selfantigens)- Exogenousantigens

(microbial)

- Complementactivation

(Invariable)

TypeIIHypersensitivityReactions

Clinical examples:

Glomerulonephritis (anti-glomerularbasement membrane)

Mis-matched blood transfusion

Diagnosis

- Detection of antibodies and antigens by Immunofluoresence in tissue biopsy specimens e.g. kidney, skin etc.

TypeIII:Immunecomplexhypersensitivity

n Whenanantigenreactswithanantibodytheproducttheyformiscalledanimmunecomplexwhichiscapableofinducinganinflammatoryresponse

n Immunecomplexesaredepositedintissueslikekidneys(nephritis),joints(arthritis)orbloodvessels(vasculitis)

Type III Hypersensitivity (immune–complex mediated)

• FeaturesAntibody (IgG/ or IgM) + Antigen (soluble)

- Immune – Complex formation

- Complement activation

- Attraction of inflammatory cells

TypeIIIReactions

Type III Hypers. ReactionsClinical examples:

Glomerulonephritis: Rheumatoid arthritis, SLE

Diagnosis of Type III Hypers. Reactions

Demonstration of specific immune complexes in the blood or tissues by:

Immunofluoresence

TypeIVhypersensitivityreactions(DelayedHypersensitivity)

• Features• Cellmediatedimmuneresponse

– AntigendependentTcell(CD4generallyandCD8occasionally)activationviaMHCClassIorII

• Activatedmacrophages• Delayedonset(2-4days)• Abnormalcellularresponse

– (Granuloma formation)

Mediators released by TDTH cells

Development of DTH Response

Sensitization phase:1-2 week period

Effector phase:24-72 hours

Effector cells(activated macs)act non-specifically

Pathophysiology of Contact dermatitis.

Type IV clinical examples:

Contact dermatitis

TB granuloma(persistent antigen)

Diagnosis (Type IV)

1. Delayed skin test (Mantoux test)

2. Patch test (Contact dermatitis)

3. Lymphocyte transformation test

Skin Patch Test

TakeHomeMessage

• 1. TypeI(IgE),II(IgG)andIII(IgG)hypersensitivityreactionsaremediatedbyantibodies whereasTypeIVhypersensitivityreactionisacellmediatedimmuneresponse.

• 2. Hypersensitivityreactionsareundesirable,excessive,andaberrant immuneresponsesassociatedwithdisorderssuchasallergy,autoimmunityandchronicinflammation.